Cell therapy holds significant potential for the reconstruction and regeneration of craniofacial defects and deformities. A current limitation of cell therapy is that the mode of delivering cells to the defect is crude and non-specific to the surgical site. Alternatively, an ideal approach would be one that is standardized enough to be reproducible, yet adaptable enough to be patient- and defect-specific. To this end, we have preliminary evidence which suggests that MSCs can be predictably isolated from alveolar bone marrow (aBMSCs), using a simple, standardized, reproducible technique. Additionally, we have demonstrated the feasibility of creating pre-shaped, patient-specific scaffolds through additive manufacturing. Our hypothesis is that clinical craniofacial bone defects can be regenerated through stem cell transplantation on 3-dimensional (3-D) printed scaffolds produced in the morphological dimensions of patient-specific craniofacial defects. To test these hypotheses, the project proposed has three Specific Aims. In SA1, we will optimize the physical and mechanical properties of 3-D scaffolds to support cell seeding, attachment, growth, and differentiation of aBMSCs and that will remain stable at the time of placement into clinical bone defects. SA2 will evaluate the preclinical bone regenerative potential of aBMSCs on customized scaffolds using clinically relevant orthotopic model systems. Finally, in SA3, we will determine the feasibility an safety of using personalized 3D printed scaffolds for delivery of autologous aBMSCs to craniofacial jawbone defects in humans. Findings of the proposed study will significantly advance clinical cell therapy approaches for craniofacial regeneration. Additionally, it would serve as an important platform for development of other personalized regenerative approaches using the powerful tool of additive manufacturing.